Impact of early proactive therapeutic drug monitoring on the durability and efficacy of infliximab therapy in pediatric inflammatory bowel disease: a multicenter open-label randomized-control trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Istituto Di Ricovero E Cura A Carattere Scientifico Materno Infantile Burlo Garofolo

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06], Diseases [C] - Immune System Diseases [C20]

Decision date (initial)

2024-10-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-517759-11-00

EudraCT number

2021-003220-32

ClinicalTrials.gov

NCT05280405

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

To evaluate the efficacy of E-pTDM compared to the standard IFX dosing schedule in improving IFX durability and efficacy during the first year of treatment.

Secondary objectives 6

1. To evaluate the efficacy of E-pTDM in reducing the frequency of subtherapeutic IFX concentrations,
2. To evaluate the efficacy of E-pTDM on endoscopic healing,
3. To evaluate the efficacy of E-pTDM on clinical remission at week 14
4. To evaluate the efficacy of E-pTDM on clinical and biochemical remission at week 14
5. To evaluate the efficacy of E-pTDM in reducing the frequency of ATI
6. To evaluate the efficacy of E-pTDM in reducing the frequency of infusion reactions

Conditions and MedDRA coding

Inflammatory Bowel Disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Anti-TNF naïve children and adolescents, 6-17 years, with a diagnosis of IBD confirmed by a prior endoscopic biopsy that is consistent with the diagnosis
2. Indication to start anti-TNF therapy in accordance with current pediatric guidelines for the treatment of pediatric IBD,
3. Active inflammation supported by CRP > 5mg/L and /or FC > 150 μg/g before the 1st IFX dose

Exclusion criteria 11

1. Patients who are not able or willing to sign informed consent
2. Stenosing or penetrating disease requiring surgery, abdominal abscess, symptomatic stricture,
3. Abdominal surgery within the previous 6 months,
4. Acute severe UC attack defined by a PUCAI score ³ 65,
5. Infective contraindication to IFX treatment including positive tuberculin skin test or Quantiferon-TB test, recent opportunistic infection, infection with hepatitis B (HBV), C (HCV), human immunodeficiency virus (HIV),
6. Hypersensitivity to the active substance, to other murine proteins, or to any of the excipients,
7. Moderate or severe heart failure (NYHA class III/IV),
8. Previous exposure to anti-TNF;
9. Exposure to concomitant prohibited medications including other biologics (including but not limited to ustekinumab, vedolizumab, abatacept, anakinra..), thalidomide, investigational drugs
10. Pregnancy or lactation (se paragraph 4.4 Pregnancy testing and contraception)
11. Current cancer

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary composite endpoint is the frequency of IFX discontinuation, due to treatment failure or adverse events, or need for treatment intensification due to non-response or LOR during the first year of treatment.

Secondary endpoints 9

1. The cumulative probability of IFX discontinuation
2. The cumulative probability of LOR
3. Subtherapeutic IFX concentrations,
4. Occurrence of ATI
5. Occurrence of infusion reactions
6. Endoscopic remission at 54 weeks
7. Treatment response at the end of induction between 12-14 weeks
8. Clinical remission at week 14
9. Clinical and biochemical remission at week 14

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Istituto Di Ricovero E Cura A Carattere Scientifico Materno Infantile Burlo Garofolo

Sponsor organisation

Istituto Di Ricovero E Cura A Carattere Scientifico Materno Infantile Burlo Garofolo

Address

Via Dell' Istria 65/1

City

Trieste

Postcode

34137

Country

Italy

Scientific contact point

Organisation

Istituto Di Ricovero E Cura A Carattere Scientifico Materno Infantile Burlo Garofolo

Contact name

Sara Lega

Public contact point

Organisation

Istituto Di Ricovero E Cura A Carattere Scientifico Materno Infantile Burlo Garofolo

Contact name

Sara Lega

Locations

1 EU/EEA country · 10 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications